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Research Paper
RIα Influences Cellular Proliferation in Cancer Cells by Transporting RFC40 into the Nucleus
Rakhee S. Gupte, Piotr Pozarowski, Jerzy Grabarek, Frank Traganos, Zbigniew Darzynkiewicz and Marietta Y. W. T. Lee
volume 4 | issue 4
April 2005Pages: 439-437
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The regulatory subunit (RIα) of cAMP-dependent Protein kinase A (PKA) is overexpressed in a variety of tumors and carcinomas such as renal cell carcinomas, pituitary tumors of the rat, malignant osteoblasts, colon carcinomas, serous ovarian tumors and primary human breast carcinomas. However, the direct relation between overexpression of RIα and malignancy is still unclear. We have recently identified a novel interaction between RIα and RFC40, the second subunit of Replication Factor C (RFC), and have demonstrated that this interaction may be associated with cell survival. Coincidentally, RFC40 is overexpressed in gestational trophoblastic diseases such as choriocarcinomas. This study was undertaken to investigate a possible functional role for both these proteins together, in DNA replication and cellular proliferation. In the course of this study, a non-conventional nuclear localization signal was identified for RIα. Nuclear transport of RFC40 was found to be dependent on RIα, and this transport appeared to be a crucial step for cell cycle progression from G1 to S phase. Impairment in the nuclear transport of RFC40 by RIα arrested cells in G1 phase. These findings provide evidence for a previously unknown mechanism for the nuclear transport of RFC40, and also for a novel mechanism for cellular proliferation.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.